Organ-specific allergen challenges in airway allergy: Current utilities and future directions.

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.

An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen.

BACKGROUND: Cats are the major source of indoor inhalant allergens after house dust mites. The global incidence of cat allergies is rising sharply, posing a major public health problem. Ten cat allergens have been identified. The major allergen responsible for symptoms is Fel d 1, a secretoglobin and not a lipocalin, making the cat a special case among mammals. MAIN BODY: Given its clinical predominance, it is essential to have a good knowledge of this allergenic fraction, including its basic structure, to understand the new exciting diagnostic and therapeutic applications currently in development. The recent arrival of the component-resolved diagnosis, which uses molecular allergens, represents a unique opportunity to improve our understanding of the disease. Recombinant Fel d 1 is now available for in vitro diagnosis by the anti-Fel d 1 specific IgE assay. The first part of the review will seek to describe the recent advances related to Fel d 1 in terms of positive diagnosis and assessment of disease severity. In daily practice, anti-Fel d 1 IgE tend to replace those directed against the overall extract but is this attitude justified? We will look at the most recent arguments to try to answer this question. In parallel, a second revolution is taking place thanks to molecular engineering, which has allowed the development of various forms of recombinant Fel d 1 and which seeks to modify the immunomodulatory properties of the molecule and thus the clinical history of the disease via various modalities of anti-Fel d 1-specific immunotherapy. We will endeavor to give a clear and practical overview of all these trends.

Peanut gastrointestinal delivery oral immunotherapy in adolescents: Results of the build-up phase of a randomized, double-blind, placebo-controlled trial (PITA study).

BACKGROUND: Oral immunotherapy to peanut is effective in desensitizing patients but has significant side effects including anaphylaxis and gastrointestinal symptoms. In most protocols, peanut is administered in a vehicle food. OBJECTIVE: In an exclusively adolescent population, we tested a new approach using sealed capsules of peanut (gastrointestinal delivery oral immunotherapy or GIDOIT) to bypass the upper gastrointestinal tract. The primary aim was to assess the efficacy of the oral build-up phase of GIDOIT and the secondary aim to analyse its safety. METHODS: Adolescents with a history of a clinical allergic reaction after peanut ingestion were included in a 2-armed, parallel-design, individually randomized, double-blind, placebo-controlled, multicentre trial after a positive double-blind placebo-controlled oral food challenge (DBPCFC1). A central randomization centre used computer-generated tables to allocate treatments. Peanut (or placebo) capsules were ingested daily over a period of 24 weeks with increments every 2 weeks from 2 to 400 mg of peanut protein (pp). Primary outcome was tolerance of 400 mg of pp at DBPCFC2. RESULTS: Thirty patients were included between September 2013 and May 2014. At DBPCFC2, unresponsiveness to 400 mg of pp was achieved in 17/21 peanut group patients (2 withdrawn patients) and 1/9 in the placebo group (Intention-to-treat analysis, P < .001, absolute difference = 0.7, 95%IC 0.43 0.96). Oropharyngeal symptoms were equally frequent in both groups. No dysphagia or other signs of eosinophilic oesophagitis occurred. Digestive adverse events (AE) were more frequent in the treated group (P = .02), but mild and without compliance issues. Only one severe advent event led to withdrawal in a patient who ingested twice the investigated treatment. Peanut-specific humoral immune responses were modulated. CONCLUSION: The GIDOIT protocol demonstrated clinical and immunological efficacy and had an acceptable level of safety with weak oropharyngeal symptoms, no dysphagia, mild digestive events and few severe systemic AE.

[Atopic keratoconjunctivitis: One allergy may mask another. A clinical observation with two types of hypersensitivity reactions: IgE-mediated and non-IgE-mediated]. / Kératoconjonctivite atopique : une allergie peut en cacher une autre. À propos d'une observation clinique avec hypersensibilité IgE médiée et hypersensibilité non IgE médiée.

Allergies are frequently implicated in ophthalmologic practice. These typically benign allergies can be potentially severe for the ocular surface and have an impact in everyday life. We relate, through a case of keratoconjunctivitis involving 2 types of hypersensitivity, the various triggers and therapeutic choices to allow a more effective treatment.

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

Diagnostic tools in ocular allergy.

Ocular allergy (OA) includes a group of common and less frequent hypersensitivity disorders frequently misdiagnosed and not properly managed. The diagnosis of OA is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when identification of the specific allergen is required. To date, no specific test is available for the diagnosis of the whole spectrum of the different forms of OA. The lack of recommendations on diagnosis of OA is considered a medical need not only for allergists but also for ophthalmologists. This position paper aims to provide a comprehensive overview of the currently available tools for diagnosing OA to promote a common nomenclature and procedures to be used by different specialists. Questionnaires, sign and symptom grading scales, tests, and potential biomarkers for OA are reviewed. We also identified several unmet needs in the diagnostic tools to generate interest, increase understanding, and inspire further investigations. Tools, recommendations, and algorithms for the diagnosis of OA are proposed for use by both allergists and ophthalmologists. Several unmet needs in the diagnostic tools should be further improved by specific clinical research in OA.

Conjunctival allergen provocation test : guidelines for daily practice.

Conjunctival allergen provocation test (CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)-triggering symptoms in IgE-mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half-life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum-specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information.

[Management of allergic conjunctivitis. An observational study among ophthalmologists]. / La prise en charge de la conjonctivite allergique. Enquête observationnelle auprès des ophtalmologistes.

PURPOSE: To describe the management of allergic conjunctivitis in private ophthalmology practice and to evaluate the collaboration between ophthalmologists and allergists. PATIENTS AND METHODS: Multicenter retrospective study. Each ophthalmologist was required to collect demographic and clinical data from the records of 10 patients with a 2- to 3-year history of allergic conjunctivitis. RESULTS: A total of 353 records were interpretable, corresponding to 885 visits. Slightly more than 60% of patients had a history of allergy (rhinitis, asthma or cutaneous allergy), and 40% of patients had had allergy testing. Fewer than 2% of patients had seen an allergist. Analysis of presenting symptoms reveals that itching, burning, tearing, photophobia and discomfort led frequently to the diagnosis of allergic conjunctivitis. This was confirmed through the interview concerning the circumstances of symptom development (most frequently involving exposure to trees and flowers) and ophthalmologic examination (presence of hyperemia, follicles, watery discharge, chemosis). The presence of non-specific symptoms such as ocular dryness was relatively frequent in association with perennial conjunctivitis. Over 95% of patients were given a topical treatment while fewer than 10% were referred to an allergist. CONCLUSION: Allergic conjunctivitis, particularly seasonal, is easily identifiable by an ophthalmologist. Perennial and more serious forms of conjunctivitis could be referred to an allergist more frequently.

Ocular allergy: recognizing and diagnosing hypersensitivity disorders of the ocular surface.

Ocular allergy includes several clinically different conditions that can be considered as hypersensitivity disorders of the ocular surface. The classification of these conditions is complex, and their epidemiology has not been adequately studied because of the lack of unequivocal nomenclature. Ocular allergy symptoms are often, but not always, associated with other allergic manifestations, mostly rhinitis. However, specific ocular allergic diseases need to be recognized and managed by a team that includes both an ophthalmologist and an allergist. The diagnosis of ocular allergy is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when the identification of the specific allergic sensitization is required for patient management. The aims of this Task Force Report are (i) to unify the nomenclature and classification of ocular allergy, by combining the ophthalmology and allergy Allergic Rhinitis and its Impact on Asthma criteria; (ii) to describe current methods of diagnosis; (iii) to summarize the therapeutic options for the management of ocular allergic inflammation.

[The role of lung volume measurements by plethysmography in the follow-up of asthma in children]. / Intérêt de la mesure des volumes pulmonaires par pléthysmographie corporelle dans le suivi de l'asthme de l'enfant.

In asthmatic children, control of the disease is perfect when no symptoms occur and lung function is normal. The aim of this study is to analyse the role of plethysmography in the follow-up of asthmatic children. We present the results of a retrospective study of lung function (plethysmography and forced expiratory flow) in about 100 asthmatic children aged five to 16years. FEV1/FVC less than 80% predicted was considered as pathological (airflow obstruction). The ratio RV/TLC was considered pathological if greater than 30% and RV was considered pathological if greater than 120% (lung hyperinflation). Bronchodilator reversibility was performed in all patients. All patients were studied in a stable condition. None had developed any asthmatic exacerbations during the past month. We found a significant correlation between the residual volume/total lung capacity (RV/TLC) ratio and, on one hand: FEV1 (p<0.0001, R=-0.374), and on the other hand FEV1/FVC (p=0.07, R=-0.182) or forced expiratory flow 25-75 (p=0.03, R=-0.216). When comparing children with (n=40) and without (n=60) lung hyperinflation, we noticed more diurnal symptoms (30/40 vs 10/60, p=0.05), lower weight (33.9kg vs 41.8kg, p<0.05) and lower body mass index (16.9kg/m(2) vs 18.4kg/m(2), p<0.01). Among the children with defined airway obstruction, 49% also had lung hyperinflation. Twenty-three children had normal forced expiratory ratios but an increase of the ratio RV/TLC or of RV. When compared with children without lung hyperinflation, the age at diagnosis was significantly lower (3.9+/-1.9years vs 6.2+/-3.1years, p<0.01) and weight slightly lower (31+/-10kg vs 40+/-11kg, p=0.04). In conclusion, the use of plethysmography and thus the evaluation of pulmonary hyperinflation contributed to a better appreciation of the asthmatic phenotype in children.

Oral food challenge in children: an expert review.

Oral food challenges are indicated for the diagnosis of food allergy and the double-blind, placebo-controlled oral food challenge is considered the gold standard diagnostic method in children with suspected food allergy. This practice parameter for oral food challenges in children was prepared by a workgroup at the request of the French Society for Allergology and Clinical Immunology (SFAIC) and the French Paediatric Society for Allergology and Pulmonology (SP2A). We aimed to develop practical guidelines for oral food challenges in children for the diagnosis of suspected food allergy or the evaluation of food tolerance. We also considered the safety measures to be implemented during testing and management of the potentially serious allergic reactions that may arise during the test. The strength of the recommendations was established, using the GRADE evidence-based approach. We considered four issues: (1) the selection of children for oral food challenges (indications and contraindications); (2) the procedure used (material, where the test should be carried out, technique and management of reactions); (3) interpretation of the test and (4) consequences of the test.

[Childhood allergic conjunctivitis: the allergist's point of view]. / Conjonctivites allergiques de l'enfant: le point de vue de l'allergologue.

Allergic conjunctivitis is one of the most frequent reasons for a child's consultation with an ophthalmologist. Once the diagnosis of conjunctivitis is made and the clinical form is clearly established, the search for a cause is the most complicated step. Consultation with an allergist is necessary, in particular when questioning the patient points toward an allergic cause or brings up conditions suggestive of atopic disease. Ocular allergy can follow a type I hypersensitivity, i.e., mediated by IgE: most frequently this is acute and chronic allergic conjunctivitis. Demonstrating the allergen requires prick tests, which are easy to carry out and painless; their sensitivity is currently satisfactory. In vitro tests can complete the workup. In case of doubt on the allergen responsability for allergy, an allergenic provocation test can confirm or refute the allergen's involvement. Ocular allergy can also stem from a type IV mechanism, i.e., a cell-mediated mechanism such as in contact allergy involving different topical substances. In these cases, the clinical aspect and the patient's history may require consultation with a dermatologist-allergist for patch tests. To adapt practices when encountering conjunctivitis in a child, the ophthalmologist should be familiar with the allergens that may set off a conjunctivitis episode. Knowledge of the mechanisms at play also helps direct the examination toward allergy or another cause. In all these steps, collaboration between the ophthalmologist and the allergist is indispensable.

[Conjunctival provocation test: recommendations]. / Le test de provocation conjonctival: recommandations pratiques pour le diagnostic des conjonctivites allergiques.

The diagnosis of ocular allergy, which has become a real public health problem occurring in 25% of the general population and continues to rise, requires allergic testing. Skin and blood tests combined with interviewing the patient demonstrate sensitivity to one or more antigens. However, while allergic testing and interviews generally reveal the cause of the symptoms, only the conjunctival provocation test (CPT) provides clear evidence of a functional relation between the conjunctival pathology and exposure to the antigen. Since there is still no validated consensus regarding the criteria for positivity of the CPT in routine practice, the working group attempted to establish the major guidelines for conducting the test, to standardize approaches and pinpoint areas of uncertainty. The group established a consensus regarding the conditions for using the test (patient selection, allergens to be tested, usable concentrations, the test protocol, the signs and symptoms to be assessed, interpretation of results, follow-up) and identified two distinct patient groups (outpatients and hospitalized patients) in whom test-taking conditions are different. The outpatient group includes patients suffering from benign forms of conjunctivitis (acute, seasonal, or chronic) and those sensitive to the usual allergens (mainly domestic and airborne). In these cases, the test is given in a medical setting with an allergologist or an ophthalmologist who instills the drops relatively rapidly. The criterion for positivity is the extent of the pruritus. On the other hand, in the hospital population, which is composed of patients suffering from vernal conjunctivitis, the attempt to establish the triggering factor requires a more elaborate protocol carried out in an ophthalmologic setting and based on the association of a range of clinical and biological factors. The deliberations of the working group should lead to the standardization of the CPT procedure for diagnostic purposes.

[Implantation of preserved human amniotic membrane for the treatment of shield ulcers and persistent corneal epithelial defects in chronic allergic keratoconjunctivitis]. / Greffe de membrane amniotique et traitement des ulcères de cornée lors des kératoconjonctivites chroniques allergiques.

PURPOSE: To determine whether amniotic membrane implantation is a safe and effective alternative treatment for shield ulcers and persistent corneal epithelial defects associated with ulcers in chronic allergic keratoconjunctivitis (vernal or atopic keratoconjunctivitis). METHODS: Amniotic membrane implantation was performed in four consecutive patients with persistent corneal epithelial defects or vernal plaques unresponsive to conventional medical treatment lasting an average of 18 weeks. Surgery was done under general anesthesia using amniotic membrane as a therapeutic contact lens. RESULTS: A significant decrease in symptoms and complete reepithelialization of the corneal ulcers were observed in all cases within the first 7 days. These remained stable during a mean follow-up of 12 weeks, with no intraoperative or postoperative complications. Early detachment occurred in all cases with no negative consequences on ulcer healing. CONCLUSION: Patients with severe chronic allergic keratoconjunctivitis derive benefits from amniotic membrane implantation used as a therapeutic contact lens in the treatment of persistent corneal epithelial defects and vernal plaques unresponsive to conventional medical treatment.

High magnesium concentration in vitro decreases human leukocyte activation.

In view of experimental data suggesting that pharmacological magnesium (Mg) therapy could be expected to temper hypersensitivity, the aim of the present study was to assess the effect of in vitro high Mg concentration (8 mmol/l vs. 0.8 mmol/l) on human leukocyte activation. The first experiment in nine healthy volunteers was performed on total leukocyte suspension containing 82 +/- 4 per cent of neutrophils. The results demonstrate the inhibitory effect of high Mg concentration as shown by the significant reduction of superoxide anion production following phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP) activation. Moreover, neutrophils activated with fMLP showed an increased respiratory burst when incubated in low Mg concentration (0.2 mmol/l) as compared to normal Mg concentration (0.8 mmol/l). Similarly, high concentration of Mg resulted in a significant reduction in superoxide anion production by eosinophils in response to PMA in five eosinophilic patients. In patients showing Hymenoptera venom hypersensitivity, high Mg concentration resulted in a significant reduction of sulphidoleukotrienes production by leukocytes in response to venom allergen (six patients) or in response to zymosan activated particules (fourteen patients). Taken together, the results suggests that Mg acts via a non specific mechanism and appears to be non specific to a particular cell type. As Mg counteracts calcium in many physiological and pathological processes, it is reasonable to hypothesise that extracellular Mg can diminish leukocyte activation by its calcium antagonism.

Atopy parameters in asthmatic infants.

We evaluated various atopy parameters in 44 asthmatic infants aged 1-3 years: nonspecific parameters (total IgE and eosinophilia), and specific parameters relative to 21 allergens (specific IgE and skin tests), together with tests of leukotriene release by blood leukocytes (cellular allergen stimulation test; CAST) in the presence of a mixture of 21 allergens. Thus far 17 infants have displayed no sign of atopy, but 27 met at least one criterion. Eight met nonspecific criteria, and the others single or multiple criteria. Of the 21 allergens, 20 gave rise to at least one sensitization in this population. The specific IgE was more frequently positive than the skin tests. Dissociations between the two types of specific tests were practically systematic. Different phenotypes based on the chosen parameters were individualized, demonstrating heterogeneity in the expression of atopy in these young infants. The polyvalent CAST was positive only when other criteria of atopy were also positive (specific IgE and/or skin tests), and the range of intensity of the responses obtained supports reactivity rather than sensitization.

[Vernal keratoconjunctivitis in the child. Clinical and complementary study apropos of 22 cases]. / Kérato-conjonctivites vernales de l'enfant. Etude clinique et complémentaire à propos de 22 cas.

PURPOSE: Vernal kératoconjunctivitis was studied in a population of 22 children aged 3 to 14 years and followed up in an allergy and ophthalmology outpatient clinic. The role of allergy and the severity of inflammation where assessed by a systematic exploration, which combined a detailed allergy evaluation and blood and lacrimal sampling. MATERIALS AND METHODS: Allergy criteria chosen and recorded in 9 cases are: an increase of total IgE over the higher limit for the age, a positive skin prick test to one allergen, a positive serum specific IgE dosage (> 0.35 IU/mL) of specific IgE. Conjunctival allergy was present in 6 of the 9 children with a positive allergenic provocation test, or with a high local production of total IgE and a lacrimal/serum eosinophilic cationic protein ratio greater than one. RESULTS: Criteria used for supporting the IgE mediated hypersensitivity diagnosis are discussed: they have to be very strict to eliminate false positive results. Allergen involvement can only be evidenced by a specific provocation test. When evidenced as described, limbic or palpebral conjunctivitis had the same frequency. Lacrimal ICAM 1 levels seemed to be higher (p < 0.05) in the severe limbal forms (24.7 +/- 3 pg/mL) than in the palpebral ones (8.1 +/- 6.5 pg/mL). Interpretation of biological parameters evidencing conjunctival inflammation is more difficult. CONCLUSION: Allergic involvement in child vernal keratoconjunctivitis can only be assessed through a detailed evaluation, leading to a specialised ophthalmic and allergic management. A specific treatment can then be established, based on allergen eviction and possibly on specific immunotherapy (5 cases). H1 antihistamin treatments are dedicated only to children with a positive allergic evaluation.

[Epidemiologic follow-up of subjects taking a cure in thermal spas: apropos of a 2-year experience in Bourboule and Saint-Nectaire]. / Le suivi épidémiologique des curistes dans les stations thermales: à propos de deux ans d'expérience à la Bourboule et à Saint-Nectaire.

We tried to find out if a controlled sentinel system can be used in a hot spring spa to determine the level of incidents encountered by cure takers and to alert in case of epidemiological events. After two years of experiences in two different thermal resorts, we conclude that such systems may operate and may be extended to other hot spring spas. Among the incidents declared, some cannot be explained by a reactivation of the chronic disease justifying the cure and we pointed out the role of places and periods of cure takers' meeting.

[Treatment of respiratory and ORL diseases with mineral waters in children]. / Crénothérapie des affections respiratoires et ORL de l'enfant.

Many questions arise when a paediatrician prescribes thermal treatment. Answers to these questions have come to light in recent literature. For paediatric indications, thermal treatment is dominated by asthma and its allergic equivalents. In such cases, sodium chloride and bicarbonated spas are used. Such indications are based on the research of the Pasteur Institute for Le Mont-Dore spa and on different modifications of intracelllular enzymes and increase of resistance to hypoxy incited by the La Bourboule spa. The waters in the spas of the Pyrenees contain sulphur, and are mainly used for the treatment of chronic or repeated ENT infections. Fundamental studies in favour of thermal treatment have only aroused indirect views. Following the enquiry made by the French National Health Service on 3,000 patients over a period of 3 years from 1983, it was found that this treatment reduces medical consumption, doctor's visits and hospital care in many cases. However no double-blind research could be performed despite the desire of several spas. These spas improve either the quality of the final product or the strict hygiene level in the thermal installations, and also the sanitary educational measures associated with thermal treatment.